Cutaneous Photobiology. The Melanocyte vs. the Sun: Who Will Win the Final Round?

Abstract

Solar ultraviolet radiation (UV) is a major environmental factor that dramatically alters the homeostasis of the skin as an organ by affecting the survival, proliferation and differentiation of various cutaneous cell types. The effects of UV on the skin include direct damage to DNA, apoptosis, growth arrest, and stimulation of melanogenesis. Long-term effects of UV include photoaging and photocarcinogenesis. Epidermal melanocytes synthesize two main types of melanin: eumelanin and pheomelanin. Melanin, particularly eumelanin, represents the major photoprotective mechanism in the skin. Melanin limits the extent of UV penetration through the epidermal layers, and scavenges reactive oxygen radicals that may lead to oxidative DNA damage. The extent of UV-induced DNA damage and the incidence of skin cancer are inversely correlated with total melanin content of the skin. Given the importance of the melanocyte in guarding against the adverse effects of UV and the fact that the melanocyte has a low self-renewal capacity, it is critical to maintain its survival and genomic integrity in order to prevent malignant transformation to melanoma, the most fatal form of skin cancer. Melanocyte transformation to melanoma involves the activation of certain oncogenes and the inactivation of specific tumor suppressor genes. This review summarizes the current state of knowledge about the role of melanin and the melanocyte in photoprotection, the responses of melanocytes to UV, the signaling pathways that mediate the biological effects of UV on melanocytes, and the most common genetic alterations that lead to melanoma.

The Regulation of Skin Pigmentation

“…Other melanogenic factors produced by keratinocytes in response to UV include SCF and NGF. The tanning response also relies on stimulation of secretion of NGF by keratinocytes, which prevents melanocyte apoptotic cell death following UV exposure (34). Stimulation of p53 in keratinocytes by UV increases expression of the POMC gene, leading to increased secretion of ␣MSH and stimulation of MC1R function in neighboring melanocytes (35).…”

USF : un régulateur essentiel de la transcription

“…Parmi elles, les rayonnements ultraviolets constituent le plus important de ces dangers, à l'origine de pathologies cutanées. La pigmentation permet la protection de la peau contre les rayonnements UV, la photo-can- [21]. Alors que le facteur de transcription Mitf intervient dans la pigmentation constitutive [22], le facteur de transcription USF-1, phosphorylé par la kinase p38 en réponse au stress UV, est impliqué dans la réponse pigmentaire [23,24].…”

Antioxidant Defense and UV-Induced Melanogenesis: Implications for Melanoma Prevention

“…For the delayed response, pigmentation can be generated by both UVB and UVA radiation and correlated to proliferation of melanocytes, increased transfer of melanosomes to keratinocytes and elevated synthesis of melanin. An induction of melanogenesis in response to UVR also depends on different melanocyte cell types, e.g., lightly-pigmented or darkly-pigmented cells (Kadekaro et al, 2003). Melanogenesis has long been recognized to serve as a major defense mechanism to protect the skin against damaging effects of UVR as both eumelanin and pheomelanin can absorb UVR and have antioxidant properties capable of limiting the penetration of UVR into the skin (Meredith & Sarna, 2006).…”